Human papilloma virus (HPV) is a non-enveloped small double-stranded circular DNA virus belonging to polyomavirus subfamily of papova virus family. HPV can be spread through intimate contact among human beings, leading to such lesions in the infected persons as verruca vulgaris on the skin and condylomata acuminata around the anus and genitalia, which are ranked as sexually transmitted diseases. The results of investigation published by the International Agency for Research on Cancer in 1995 showed that HPV is closely responsible for cervical cancer. It is thus clear that HPV has become a pathogen that is severely harmful to human health. Therefore, it is much significant to develop highly efficient and inexpensive HPV vaccines for the prevention of cervical cancer in women and the sexually transmitted diseases caused by HPV infection.
More than 100 subtypes of HPV have been identified currently. Nearly 100% of the cervical cancer patients can be detected positive for the presence of high-risk HPV DNA in the pathologic tissues by using sensitive detection methods. In terms of the relationship between HPV subtypes and malignancies in genital tract of female patient, HPV can be classified into low-risk type and high-risk type. HPV6, 11, 34, 40 and 42 and the like are low-risk HPV subtypes, typically found in benign cervical lesions such as cervical condylomas and mild atypical hyperplasia of cervical epithelium; while HPV 16, 18, 31, 33, 35, 39, 45 are high-risk HPV subtypes, mostly found in severe atypical hyperplasia of cervical epithelium as well as cervical cancer. A series of studies on different human populations have substantiated that HPV 16 and 18 infections in genital tract are more highly associated with the occurrence of cervical cancer than other risk factors. Among cervical cancer patients, about 50 to 60% of the cases are caused by HPV 16 infection, about 14% by HPV 18, about 8% by HPV 45, and about 5% by HPV 31, with the remaining 23% of the cases caused by other HPV subtypes.
HPV is non-enveloped and globular in shape with a diameter of about 45 to 55 nm, having an icosahedrally symmetric deflective capsid consisting of 72 capsid particles. The virion capsid is essentially comprised of major capsid proteins (L1) and minor capsid proteins (L2). After being expressed in cells, major capsid proteins L1 can be self-assembled into capsid particles called virus-like particles (VLPs).
A normal woman has a life-time accumulative probability of about 40% for cervical infection by at least one subtype of HPV during her whole life. Therefore, it is of great importance to develop suitably-priced and advantageously protective vaccines against cervical cancer, especially vaccines against HPV 16 and HPV 18, for lowering the morbidity and mortality of cervical cancer in women.
Although some vaccines have been developed against HPV in the prior art, these vaccines generally have the problems of low expression efficiency of HPV protein, low activity of the expressed protein, inability of the protein to assemble into virus-like particles or undesirability of the immunological effect of the assembled particles. Consequently, there exists a need in the art for improved HPV vaccine products.